PONE-D-24-04504Association of Urinary Excretion Rates of Uric Acid with Biomarkers of Kidney Injury in Patients with Advanced Chronic Kidney DiseasePLOS ONE

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Section Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors evaluated the relation of excreted uric acid with some kidney injury biomarkers in order to use such parameter as a marker of progression of kidney disease. Data is solid and well presented. I would ask to check the journal directives for presenting the paper.

The manuscript is overall well written, but with some typos, which makes me recommend a detailed review on the text to double-check if there are more mistakes other than the ones listed bellow:

- Along the introduction, you wrote Crystalline with an I instead of y.

- On the fifth paragraph of the discussion, you wrote progression in Spanish.

- On the seventh paragraph of discussion, you wrote questionable with double n.

- In the same paragraph, you bring a word cae which I believe should be case.

- The last phrase of the last paragraph needs to be rewritten. Some words might be missing.

- In reference 8, allopurinol is written with a single letter l.

Reviewer #2: The authors address the apparent paradox of a weak correlation between hyperuricemia and the progression of chronic kidney disease (CKD) by seeking an evaluation system that better reflects the roles of uric acid (UA) in CKD pathogenesis. Their findings suggest that urinary excretion rates of UA may serve as a more precise marker for identifying UA-related kidney injury.

Major Comments:

1. The results from tables 7 to 9 indicate significant differences primarily in the 4th quartile, suggesting that only extremely high urinary uric acid concentrations correlate well with urinary markers of kidney injury. However, the presence of other symptoms due to elevated urinary uric acid levels may confound the assessment of UA-related kidney damage. Hence, it is crucial to ascertain whether the authors included criteria for asymptomatic hyperuricemia in patient recruitment. If so, clarification regarding these criteria is warranted.

2. It appears that Figure 3 and Figure 4 are identical except for the x-axis title.

3. Could the authors provide the urinary creatinine levels? Since all scrutinized kidney injury markers are normalized by creatinine, this information is essential for contextualizing the findings.

4. The authors should provide more descriptive interpretations of their results rather than solely presenting statistical analysis tables in the manuscript.

Minor Comments:

1. Page 2, line 5, "resuts" should be "results."

2. Page 3, line 13, "hiperuricemia" should be "hyperuricemia."

3. From table 5 to table 9, "4rd quartile" should be "4th quartile."

4. Please ensure consistency in number formatting across different tables; some numbers use ".", while others use ",".

5. Please provide the catalogue numbers of the ELISA kits used in the manuscript.

6. In the methods section, the authors should include the formulas used for calculating eGFR, creatinine clearance, urea clearance, and uric acid clearance, respectively.

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Reviewer #1: No

Reviewer #2: No

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Association of Urinary Excretion Rates of Uric Acid with Biomarkers of Kidney Injury in Patients with Advanced Chronic Kidney Disease

PONE-D-24-04504R1

Dear Dr. Pérez Fontán,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Partha Mukhopadhyay, Ph.D.

Section Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Authors responded to all requests in a satisfactory fashion, and I recommend the publication of this manuscript.

Reviewer #2: Please ensure consistency in number formatting in table 3; some numbers use ".", while others use ",".

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Bruno Paes Leme Ferreira

Reviewer #2: No

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